Objective: Assessment of social memory in Mecp2 mutant mice to determine if learning deficits are present in these animals
Assessment of social memory in Mecp2 308 mutant mice
Note: Social memory was significantly impaired in Mecp2 308/Y mutant males
“social memory were significantly impaired in Mecp2 308 mutant males (Mecp2 308/Y)”
Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 ( Mecp2 308 ) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2 308 mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2 308 mutant males ( Mecp2 308/Y ). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2 308/Y mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2 308/Y mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.
Mecp2 308/Y mutant males; mice expressing a truncated allele of Mecp2